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PubMed2006

Effects of abatacept in patients with methotrexate-resistant active rheumatoid arthritis: a randomized trial.

BACKGROUND: The selective co-stimulation modulator abatacept demonstrated efficacy for treating rheumatoid arthritis in early clinical studies. OBJECTIVE: To evaluate the effects of abatacept in patients with persistent, active rheumatoid arthritis despite methotrexate treatment. DESIGN: One-year, multicenter, randomized, double-blind, placebo-controlled trial (November 2002 to October 2004). SETTING: 116 centers worldwide. PATIENTS: 652 patients with active rheumatoid arthritis despite methotrexate treatment. INTERVENTION: Once-monthly infusion of a fixed dose of abatacept, approximately 10 mg/kg of body weight, or placebo. MEASUREMENTS: Co-primary end points were a 20% improvement in American College of Rheumatology (ACR) response criteria (ACR 20) at 6 months, clinically meaningful improvements in physical function, and change from baseline in joint erosion score at 1 year. RESULTS: Four hundred thirty-three and 219 patients were randomly assigned to abatacept or placebo, respectively, and 385 (89%) and 162 (74%), respectively, completed 1 year of treatment. In a modified intention-to-treat analysis, 6-month ACR 20, ACR 50, and ACR 70 responses were 67.9% for abatacept versus 39.7% for placebo (difference, 28.2 percentage points [95% CI, 19.8 to 36.7 percentage points]), 39.9% for abatacept versus 16.8% for placebo (difference, 23.0 percentage points [CI, 15.0 to 31.1 percentage points]), and 19.8% for abatacept versus 6.5% for placebo (difference, 13.3 percentage points [CI, 7.0 to 19.5 percentage points]), respectively. At 1 year, the responses increased to 73.1% for abatacept versus 39.7% for placebo (difference, 33.4 percentage points [CI, 25.1 to 41.7 percentage points]), 48.3% for abatacept versus 18.2% for placebo (difference, 30.1 percentage points [CI, 21.8 to 38.5 percentage points]), and 28.8% for abatacept versus 6.1% for placebo (difference, 22.7 percentage points [CI, 15.6 to 29.8 percentage points]), respectively (P < 0.001 for all). Physical function significantly improved in 63.7% versus 39.3% of patients (P < 0.001). At 1 year, abatacept statistically significantly slowed the progression of structural joint damage compared with placebo. Abatacept-treated patients had a similar incidence of adverse events (87.3% vs. 84.0%; difference, 3.3 percentage points [CI, -2.5 to 9.1 percentage points]) and a higher incidence of prespecified serious infections (2.5% vs. 0.9%; difference, 1.6 percentage points [CI, -0.3 to 3.6 percentage points]) and infusion reactions (acute, 8.8% vs. 4.1%; difference, 4.7 percentage points [CI, 0.9 to 8.4 percentage points]; peri-infusional, 24.5% vs. 16.9%; difference, 7.6 percentage points [CI, 1.2 to 14.0 percentage points]) compared with placebo recipients. LIMITATIONS: The study involved only 1 group of patients over 1 year. CONCLUSIONS: Abatacept statistically significantly reduced disease activity in patients with rheumatoid arthritis and an inadequate response to methotrexate. Longer treatment in different patient populations is needed to establish its appropriate role in rheumatoid arthritis.

Abatacept↗
PubMed2006

Role of abatacept in the management of rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) has been associated with significant morbidity and economic burden. Traditional pharmacotherapy (eg, NSAIDs, corticosteroids, disease-modifying antirheumatic drugs [DMARDs]) can be inadequate in controlling symptoms and disease progression. Abatacept is the first selective co-stimulation modulator approved by the US Food and Drug Administration for the management of RA. It is a fusion protein developed to modulate the T-cell co-stimulatory signal that is mediated through the CD28-CD80/86 pathway. OBJECTIVE: The objective of this manuscript was to review the clinical pharmacology, pharmacokinetic and pharmacodynamic properties, tolerability, and clinical efficacy of abatacept. METHODS: MEDLINE and International Pharmaceutical Abstracts were searched through June and May, respectively, of 2006 using the term abatacept or CTLA4-Ig. All prospective, randomized, Phase II and III trials, and their extension phases, were included. RESULTS: Phase II and III clinical trials found that abatacept, at a dose of 10 mg/kg administered as a short i.v. infusion in combination with DMARDs, was associated with significant clinical benefit in patients with active RA. After 6 months of treatment, the American College of Rheumatology (ACR) criteria for 20% clinical improvement (ACR20 response) was attained in 41.9% to 67.9% of patients who received abatacept compared with 19.5% to 39.7% of patients who received placebo (P < 0.001). The percentages of patients achieving the ACR criteria for 50% and 70% clinical improvement (ACR50 and ACR70) were 20.3% to 39.9% and 10.2% to 19.8%, respectively, in the groups that received abatacept compared with 3.8% to 16.8% and 1.5% to 6.5%, respectively, in the patients who received placebo (P = 0.03 and P < 0.001). Additionally, abatacept was found to improve disease activity, physical function, pain, and health-related quality of life (HRQOL). The most commonly reported adverse effects associated with abatacept treatment were headache (18.2%), upper respiratory tract infection (12.7%), nasopharyngitis (11.5%), and nausea (11.5%). The incidences of infections and serious infections were higher in the group that received abatacept compared with patients who received placebo (53.8% vs 48.3% and 3.0% vs 1.9%, respectively; P not reported). No significant between-group differences in mortality were found. CONCLUSIONS: Available evidence suggests that abatacept was effective in controlling symptoms and improving HRQOL in patients with active RA and an inadequate response to DMARD therapy. The most commonly reported adverse effects associated with abatacept treatment were headache, upper respiratory infection, nausea, and nasopharyngitis. Additional trials are needed to determine the long-term safety profile of this agent and whether the clinical benefits of abatacept found in the current clinical trials will be sustained over time.

Abatacept↗
PubMed2006

Abatacept.

PURPOSE: The pharmacology, pharmacokinetics, indications, clinical efficacy, adverse effects, drug interactions, dosing, and administration of abatacept are discussed. SUMMARY: Abatacept is the first drug in a new class of agents known as selective costimulator modulators. Abatacept has been shown to decrease tumor necrosis factor (TNF)-alpha, which is important to the inflammatory response. Abatacept inhibits T-cell function but does not deplete T cells. Activated T cells are important in the inflammatory cascade, ultimately leading to joint inflammation and irreversible structural damage. In patients with rheumatoid arthritis, there is chronic inflammation of the synovial tissue lining the joint capsule. Abatacept is indicated for reducing the signs and symptoms of moderate to severe rheumatoid arthritis in adult patients who have had an inadequate response to at least one disease-modifying antirheumatic drug. Studies in adult patients with rheumatoid arthritis have evaluated abatacept in patients with an inadequate response to either methotrexate or TNF-alpha blocking agents. One trial showed that abatacept produced a favorable six-month clinical response in patients who had previously failed to respond to anti-TNF-alpha therapy. In a study of concurrent abatacept and methotrexate therapy, the addition of abatacept produced favorable outcomes in patients who were not adequately responding to methotrexate alone. CONCLUSION: Abatacept, a newly approved agent for the treatment of rheumatoid arthritis, has shown promising results in patients who have had an inadequate response to other treatment modalities. Abatacept therapy should be reserved for patients who have failed other time-tested treatment modalities, including TNF-alpha antagonists. Results from ongoing postmarketing studies will help determine abatacept's place in therapy.

Abatacept↗
PubMed2006

Treatment of rheumatoid arthritis patients with abatacept and methotrexate significantly improved health-related quality of life.

OBJECTIVE: This study examined the effect of abatacept, a costimulation modulator, on the health-related quality of life (HRQOL) of patients with rheumatoid arthritis (RA). METHODS: Three hundred thirty-nine patients with RA on a background of methotrexate (MTX), who participated in a multicenter, double-blind, placebo-controlled trial, were randomized to abatacept 2 mg/kg, abatacept 10 mg/kg, or placebo. HRQOL was assessed at pretreatment, and at 3, 6, and 12 months posttreatment using the SF-36 Health Survey (SF-36). Changes in SF-36 scores from baseline to 12 months were compared across treatment and placebo groups to examine HRQOL benefits of abatacept. A link between American College of Rheumatology improvement and changes in SF-36 scores was established to demonstrate the association between HRQOL outcomes and clinical response. RESULTS: After 12 months of treatment, patients randomized to abatacept 10 mg/kg showed significantly better HRQOL outcomes overall versus patients randomized to placebo (MANOVA F = 4.71, p < 0.001) or to abatacept 2 mg/kg (MANOVA F = 1.97, p = 0.05). Differences in SF-36 change scores between abatacept 10 mg/kg and placebo groups reached statistical significance on all 8 domain scales, the 2 summary measures, and the SF-36 utility index (SF-6D). Differences in SF-36 change scores between abatacept 10 mg/kg and abatacept 2 mg/kg reached statistical significance on 5 of the 8 domain scales, the physical summary measure, and the SF-6D. Improvement in HRQOL was highly related to clinical response. CONCLUSION Abatacept 10 mg/kg plus MTX demonstrated a stronger HRQOL response than placebo plus MTX. The abatacept 2 mg/kg arm showed a very weak and transient response.

Abatacept↗
PubMed2005

Treatment of rheumatoid arthritis with the selective costimulation modulator abatacept: twelve-month results of a phase iib, double-blind, randomized, placebo-controlled trial.

OBJECTIVE: To determine the clinical efficacy, safety, and immunogenicity of abatacept (CTLA-4Ig), a selective costimulation modulator, in patients with rheumatoid arthritis (RA) that has remained active despite methotrexate (MTX) therapy. METHODS: This was a 12-month, multicenter, randomized, double-blind, placebo-controlled study. A total of 339 patients with active RA despite MTX therapy were randomly assigned to receive 10 mg/kg abatacept (n = 115), 2 mg/kg abatacept (n = 105), or placebo (n = 119). This report focuses on the results observed at month 12 of a phase IIb trial. RESULTS: A significantly greater percentage of patients treated with 10 mg/kg abatacept met the American College of Rheumatology 20% improvement criteria (achieved an ACR20 response) at 1 year compared with patients who received placebo (62.6% versus 36.1%; P < 0.001). Greater percentages of patients treated with 10 mg/kg abatacept also achieved ACR50 responses (41.7% versus 20.2%; P < 0.001) and ACR70 responses (20.9% versus 7.6%; P = 0.003) compared with patients who received placebo. For patients treated with 10 mg/kg abatacept, there were also statistically significant and clinically important improvements in modified Health Assessment Questionnaire scores compared with patients who received placebo (49.6% versus 27.7%; P < 0.001). Abatacept at a dosage of 10 mg/kg elicited an increase in rates of remission (Disease Activity Score in 28 joints of <2.6) compared with placebo at 1 year (34.8% versus 10.1%; P < 0.001). The incidence of adverse events was comparable between the groups, and no significant formation of neutralizing antibodies was noted. CONCLUSION: Abatacept was associated with significant reductions in disease activity and improvements in physical function that were maintained over the course of 12 months in patients with RA that had remained active despite MTX treatment. Abatacept was found to be well tolerated and safe over the course of 1 year. Abatacept in combination with MTX has the potential to play an important role in future RA therapy.

Abatacept↗
PubMed2006

Safety of the selective costimulation modulator abatacept in rheumatoid arthritis patients receiving background biologic and nonbiologic disease-modifying antirheumatic drugs: A one-year randomized, placebo-controlled study.

OBJECTIVE: To assess the safety of abatacept, a selective costimulation modulator, in patients with active rheumatoid arthritis (RA) who had been receiving > or =1 traditional nonbiologic and/or biologic disease-modifying antirheumatic drugs (DMARDs) approved for the treatment of RA for at least 3 months prior to entry into the study. METHODS: This was a 1-year, multicenter, randomized, double-blind, placebo-controlled trial. Patients were randomized 2:1 to receive abatacept at a fixed dose approximating 10 mg/kg by weight range, or placebo. RESULTS: The abatacept and placebo groups exhibited similar frequencies of adverse events (90% and 87%, respectively), serious adverse events (13% and 12%, respectively), and discontinuations due to adverse events (5% and 4%, respectively). Five patients (0.5%) in the abatacept group and 4 patients (0.8%) in the placebo group died during the study. Serious infections were more frequent in the abatacept group than in the placebo group (2.9% versus 1.9%). Fewer than 4% of patients in either group experienced a severe or very severe infection. The incidence of neoplasms was 3.5% in both groups. When evaluated according to background therapy, serious adverse events occurred more frequently in the subgroup receiving abatacept plus a biologic agent (22.3%) than in the other subgroups (11.7-12.5%). CONCLUSION: Abatacept in combination with synthetic DMARDs was well tolerated and improved physical function and physician- and patient-reported disease outcomes. However, abatacept in combination with biologic background therapies was associated with an increase in the rate of serious adverse events. Therefore, abatacept is not recommended for use in combination with biologic therapy.

Abatacept↗
PubMed2006

Abatacept.

Abatacept (Orencia) is the first in a new class of biologics known as selective costimulation modulators. It inhibits full activation of T cells and interacts with other cell types to affect additional mediators of the inflammatory cascade. The clinical efficacy of abatacept in patients with active rheumatoid arthritis, despite prior treatment with methotrexate or anti-tumor necrosis factor-alpha (anti-TNFalpha) therapies, has been investigated in two randomized, double-blind, placebo-controlled, multicenter, phase III trials of 6 or 12 months' duration. In these trials, patients received intravenous abatacept (fixed-dose regimen based on bodyweight) or placebo in addition to background disease-modifying anti-rheumatic drugs (DMARDs) other than anti-TNFalpha therapies. Relative to placebo, abatacept significantly improved signs and symptoms of disease assessed using American College of Rheumatology (ACR) 20, 50, and 70 criteria and specific improvement in physical function as measured by the Health Assessment Questionnaire Disability Index at 6 months and significantly slowed structural damage progression in joints at 12 months. Improvements in ACR 20, 50, and 70 response rates were maintained at the final assessment in the 12-month trial. Abatacept infusions were generally well tolerated. Acute infusion-related reactions occurred in 9% of abatacept and 6% of placebo recipients in phase III trials. Integrated safety data from five clinical trials showed that serious adverse events were reported in 13.6% of abatacept and 12.3% of placebo recipients and the incidence of serious infections was 3.0% and 1.9%. Abatacept administered with background biologic DMARDs appears to be less well tolerated than abatacept plus background nonbiologic DMARDs.

Abatacept↗
PubMed2006

Selective costimulation modulation using abatacept in patients with active rheumatoid arthritis while receiving etanercept: a randomised clinical trial.

OBJECTIVE: To investigate the efficacy and safety of abatacept in combination with etanercept in patients with active rheumatoid arthritis during a 1-year, randomised, placebo-controlled, double-blind phase, followed by an open-label, long-term extension (LTE). METHODS: Patients continued etanercept (25 mg twice weekly) and were randomised to receive abatacept 2 mg/kg (n = 85) or placebo (n = 36). As the effective dose of abatacept was established as 10 mg/kg in a separate trial, all patients received abatacept 10 mg/kg and etanercept during the LTE. RESULTS: A total of 121 patients were randomised; 80 completed double-blind treatment and entered the LTE. During double-blind treatment, the difference in the percentage of patients achieving the primary end point (modified American College of Rheumatology (ACR) 20 response at 6 months) was not significant between groups (48.2% v 30.6%; p = 0.072). At 1 year, no notable changes in modified ACR responses were observed. Subsequent to the dosing change, similar modified ACR responses were seen during the LTE. Significant improvements in quality of life were observed with abatacept and etanercept versus placebo and etanercept in five of the eight short-form 36 subscales at 1 year. More abatacept and etanercept-treated patients experienced serious adverse events (SAEs) at 1 year than patients receiving placebo and etanercept (16.5% v 2.8%), with 3.5% v 0% experiencing serious infections. CONCLUSION: The combination of abatacept (at a dose of 2 mg/kg during the double-blind phase and 10 mg/kg during the LTE) and etanercept was associated with an increase in SAEs, including serious infections, with limited clinical effect. On the basis of the limited efficacy findings and safety concerns, abatacept in combination with etanercept should not be used for rheumatoid arthritis treatment.

Abatacept↗
PubMed2005

Prophylactic administration of abatacept prevents disease and bone destruction in a rat model of collagen-induced arthritis.

Abatacept is the first in a new class of agents that selectively modulates T-cell activation by attenuating CD28-mediated co-stimulation. This study examined the effects of abatacept on disease development in a rat model of collagen-induced arthritis (CIA). The rats were treated with either abatacept (1mg/kg) or control IgG beginning at the time of induction of CIA. By day 16, significant paw swelling was observed in IgG-treated control animals that continued to increase, reaching a plateau on day 21. Prophylactic treatment with abatacept completely abrogated paw swelling throughout the study. Histopathology demonstrated a significant reduction in inflammation, cartilage destruction, bone resorption and pannus formation. Abatacept treatment resulted in 90% inhibition of circulating collagen-specific antibodies and decreased the serum expression of many cytokines and chemokines that were upregulated in diseased animals. Immunohistochemical analysis of the ankle joints demonstrated that interleukin-6 production was reduced in the tissues and the numbers of osteoclasts present in the joints were also decreased. Ankle microcomputer tomography (micro-CT) analyses dramatically demonstrated the protective effects of abatacept on bone destruction in these animals. Data presented here demonstrate that prophylactic administration of abatacept significantly inhibits the onset and progression of disease in a rat CIA model, with reductions in inflammation, inflammatory mediators, and bone and joint destruction.

Abatacept↗
PubMed2005

Abatacept for rheumatoid arthritis refractory to tumor necrosis factor alpha inhibition.

BACKGROUND: A substantial number of patients with rheumatoid arthritis have an inadequate or unsustained response to tumor necrosis factor alpha (TNF-alpha) inhibitors. We conducted a randomized, double-blind, phase 3 trial to evaluate the efficacy and safety of abatacept, a selective costimulation modulator, in patients with active rheumatoid arthritis and an inadequate response to at least three months of anti-TNF-alpha therapy. METHODS: Patients with active rheumatoid arthritis and an inadequate response to anti-TNF-alpha therapy were randomly assigned in a 2:1 ratio to receive abatacept or placebo on days 1, 15, and 29 and every 28 days thereafter for 6 months, in addition to at least one disease-modifying antirheumatic drug. Patients discontinued anti-TNF-alpha therapy before randomization. The rates of American College of Rheumatology (ACR) 20 responses (indicating a clinical improvement of 20 percent or greater) and improvement in functional disability, as reflected by scores for the Health Assessment Questionnaire (HAQ) disability index, were assessed. RESULTS: After six months, the rates of ACR 20 responses were 50.4 percent in the abatacept group and 19.5 percent in the placebo group (P<0.001); the respective rates of ACR 50 and ACR 70 responses were also significantly higher in the abatacept group than in the placebo group (20.3 percent vs. 3.8 percent, P<0.001; and 10.2 percent vs. 1.5 percent, P=0.003). At six months, significantly more patients in the abatacept group than in the placebo group had a clinically meaningful improvement in physical function, as reflected by an improvement from baseline of at least 0.3 in the HAQ disability index (47.3 percent vs. 23.3 percent, P<0.001). The incidence of adverse events and peri-infusional adverse events was 79.5 percent and 5.0 percent, respectively, in the abatacept group and 71.4 percent and 3.0 percent, respectively, in the placebo group. The incidence of serious infections was 2.3 percent in each group. CONCLUSIONS: Abatacept produced significant clinical and functional benefits in patients who had had an inadequate response to anti-TNF-alpha therapy.

Abatacept↗
PubMed2006

Improved health-related quality of life for rheumatoid arthritis patients treated with abatacept who have inadequate response to anti-TNF therapy in a double-blind, placebo-controlled, multicentre randomized clinical trial.

OBJECTIVE: Rheumatoid arthritis (RA) patients who have inadequate response to anti-tumour necrosis factor (TNF) therapy currently have treatment options that are limited and less than optimal in their risk-to-benefit ratio. Abatacept provides a new generation of RA medications that has previously been demonstrated to have positive clinical outcomes with this population. The current study sought to demonstrate the efficacy of abatacept on quality of life (QoL) for RA patients with inadequate response to anti-TNF therapy. METHODS: Patients were entered into a double-blind, placebo-controlled, multicentre randomized clinical trial, with 258 patients randomized to abatacept + disease-modifying anti-rheumatic drugs (DMARDs) and 133 patients randomized to placebo + DMARDS. The QoL was measured with the Short Form Health Survey (SF-36), Health Assessment Questionnaire (HAQ) and fatigue visual analogue scale, and was analysed with basic (ANOVA, chi-square) and multigroup growth curve techniques to assess differential change over time. RESULTS: Treatment group QoL improved significantly more than placebo on the HAQ and fatigue indices, as well as seven of the eight SF-36 scales and SF-36 physical and mental summary scores. Improvement rate was faster for abatacept than for placebo on the QoL measures, and the improvements from abatacept related to normal levels of QoL on many domains. CONCLUSION: Clinically relevant benefits of abatacept over placebo are discussed regarding improving QoL. Importantly, the larger rate of change for abatacept over placebo provides clinicians with a medication that can lead to meaningful changes in a patient's life within a few weeks, even when the patient previously failed anti-TNF therapy.

Abatacept↗
PubMed2006

Reduction of inflammatory biomarker response by abatacept in treatment of rheumatoid arthritis.

OBJECTIVE: Abatacept, a soluble selective costimulation modulator, selectively modulates T cell activation via the CD80/CD86:CD28 costimulation pathway. Data from a Phase II trial showed efficacy in patients with active rheumatoid arthritis (RA) and inadequate response to methotrexate when treated with abatacept (10 mg/kg or 2 mg/kg). To determine the mechanism of action of abatacept, we analyzed changes in the serum levels of inflammatory biomarkers in the patients enrolled in this trial. RESULTS: Following 12 months' treatment, serum levels of interleukin 6 (IL-6), soluble IL-2 receptor, C-reactive protein, soluble E-selectin, and soluble intercellular adhesion molecule-1 were significantly lower in patients receiving abatacept 10 mg/kg versus placebo. Smaller reductions in tumor necrosis factor-a and rheumatoid factor were also observed in the abatacept 10 mg/kg group compared with the placebo group. Although there was no evidence for efficacy of the 2 mg/kg dose, small reductions in inflammatory biomarkers at this dosage support the biologic effect of this therapy. CONCLUSION: These findings reveal the antiinflammatory and immunomodulatory effects of abatacept in patients with RA, and are consistent with the concept that modulating T cell activation improves clinical signs and symptoms and inhibits the progression of structural damage. These data suggest that selective modulation of the CD80/CD86:CD28 pathway with abatacept may affect several inflammatory cell types and cytokines that are involved in the proinflammatory cascade.

Abatacept↗
PubMed2006

Abatacept: A review of a new biologic agent for refractory rheumatoid arthritis for dermatologists.

Abatacept is a newly approved treatment for rheumatoid arthritis refractory to other agents. Abatacept is a fusion protein of the cytotoxic T-lymphocyte antigen (CTLA) molecule and immunoglobulin (Ig) G1 that blocks CD28. Specifically, abatacept blocks the CD80 and CD86 ligands on the surface of antigen-presenting cells that must interface with the T-cell's CD28 receptor to activate T cells. Abatacept seems to be more immunosuppressive than tumor necrosis factor alpha blockers. The combination of abatacept and a tumor necrosis factor alpha blocking agent does not seem more effective than either agent alone. Because abatacept has the ability to suppress T-cell function, it has the potential to be a treatment for psoriasis and other autoimmune conditions involving pathologic processes driven by T cells.

Abatacept↗
PubMed2006

Abatacept improves both the physical and mental health of patients with rheumatoid arthritis who have inadequate response to methotrexate treatment.

OBJECTIVE: To examine the impact of added abatacept treatment on health related quality of life (HRQoL) in patients with rheumatoid arthritis (RA) who have inadequate response to methotrexate (MTX). METHODS: The impact of abatacept treatment on HRQoL was examined in a longitudinal, randomised double blind, placebo controlled clinical trial. Effects of treatment on HRQoL were examined using repeated measures analysis of covariance and comparing rates of change in HRQoL across treatment groups. The relationship between American College of Rheumatology (ACR) clinical markers and disease duration with changes in HRQoL indicators was also examined. Finally, a responder analysis was used to examine the percentage of patients who improved by 0.5 SD in 12 months or who reached the normative levels seen in the US general population. RESULTS: Statistically significant improvements in the abatacept group relative to controls were observed across a range of HRQoL measures, including physical function, fatigue, all eight domains of the SF-36, and the physical and mental component summaries (PCS and MCS). Improvements were seen as early as day 29 for fatigue and for five out of eight SF-36 domains. By day 169, all HRQoL measures were significantly better with abatacept than with placebo. HRQoL gains were associated with greater ACR clinical improvement, and the effects were consistent for patients with different disease duration. A significantly greater percentage of patients treated with abatacept reached normative levels of PCS, MCS, physical functioning, and fatigue compared with patients treated with MTX alone. CONCLUSION: Combined abatacept and MTX treatment produces significant improvements across a wide range of HRQoL domains in patients with RA.

Abatacept↗
PubMed2005

Abatacept as add-on therapy for rheumatoid arthritis.

Abatacept is a co-stimulation blocker that inhibits T-cell activation and interrupts the process leading to inflammation in rheumatoid arthritis. Patients with severe arthritis who took abatacept with at least one other disease-modifying antirheumatic drug in six and 12-month clinical trials demonstrated statistically significant improvement in tender, swollen joints and other clinical measures compared with placebo. Mild to moderate adverse events included headache, nasopharyngitis, hypertension and back pain. The adverse events were similar to those seen in placebo groups. Abatacept should not be used in combination with other biologic agents because of reported increased rates of serious adverse events, including serious infections. With its different mechanism of action, abatacept may be an alternative add-on therapy for patients with an inadequate response to other arthritis therapies.

Antirheumatic Agents↗
PubMed2005

Abatacept: a costimulatory inhibitor for treatment of rheumatoid arthritis.

T cell costimulation is believed to be crucial in orchestrating immune responses that lead to inflammation and destruction in rheumatoid arthritis (RA). Abatacept is a novel recombinant CTLA4Ig fusion protein that selectively modulates costimulation via interrupting the CD28:CD80/86 pathway, resulting in downregulation of T cell activation and multiple ensuing effector mechanisms. Abatacept has been shown to be efficacious, either when given alone or in combination with methotrexate, in patients with active RA, including anti-TNF failures. Improvements in clinical signs and symptoms, slowing of radiological progression, and enhancement in patient function and pain have been reported in clinical trials. Infusions were well-tolerated with a favourable safety profile similar to placebo and no appreciable immunogenicity. Abatacept is the first in a new class of biological response modifiers called costimulatory blockers.

Abatacept↗
PubMed2006

Drug Insight: abatacept for the treatment of rheumatoid arthritis.

Although the development of tumor necrosis factor antagonists has improved the clinical outcome of many patients with rheumatoid arthritis (RA), some patients fail to respond to these drugs or have contraindications preventing their use. Other approaches for treating this disease are, therefore, keenly sought. As T cells promote numerous disease pathways in RA, these cells are a logical target for anti-inflammatory therapy. One of the approaches being investigated involves targeting the co-stimulatory signals that accompany antigen-derived signals involved in the activation of T cells. Abatacept is a recombinant fusion protein that interrupts the T-cell co-stimulatory signal mediated through the CD28-CD80/CD86 pathway. Several clinical trials have now confirmed the efficacy of this compound in the treatment of RA. This article discusses the proposed mechanism of action of abatacept and reviews the data from phase II and phase III clinical trials on the safety and efficacy of this drug in RA.

Abatacept↗
PubMed2005

The evolving clinical profile of abatacept (CTLA4-Ig): a novel co-stimulatory modulator for the treatment of rheumatoid arthritis.

Abatacept (CTLA4-Ig) is a novel fusion protein designed to modulate the T cell co-stimulatory signal mediated through the CD28-CD80/86 pathway. Clinical trials have provided preliminary evidence of the efficacy of this compound in the treatment of rheumatoid arthritis. This review describes the molecular and biologic bases for the use of abatacept in rheumatoid arthritis and summarizes the current clinical data on its safety and effectiveness in this disease.

Abatacept↗